PROJECT SUMMARY Age-related hearing loss (ARHL)- clinically referred to as presbycusis, is the leading neurodegenerative disorder, the number one communication problem, and one of the top three chronic medical conditions in the aged population. The long-term goal of this proposal seeks to assess the efficacy of two innovative therapies to combat ARHL: (1) systemic treatment with omega-3 essential fatty acids paired with aldosterone and (2) exposure augmented acoustic environment. Treatment efficacy will be evaluated by monitoring sensory (cochlea) and neural (brain) circuitry, as well as changes in molecular and structural biomarkers associated with ARHL. There are 2 Specific Aims in this proposal: Specific Aim 1. Determine the therapeutic effects of omega-3 essential fatty acids on the aging auditory system. Aging mice will be fed a diet rich in omega-3 fatty acids (n-3), and neural and molecular metrics will be measured, along with behavioral, physiological, and anatomical indices. Positive results would allow us to look toward pairing n-3 with aldosterone, a hormone that has shown promise in halting age-related hearing loss in animal studies at the Global Center for Hearing and Speech Research (GCHSR). Specific Aim 2. Determine the ability of augmented acoustic environments to arrest or prevent salient features of presbycusis. Enriched acoustic environments will consist of extended, controlled exposure to specific artificially generated sounds presented in free field in the animal holding environment (vivarium). Outcome measures will index peripheral and central components of ARHL at systems, cellular, and molecular levels. The multidisciplinary team at the GCHSR is making significant strides toward translational advances in the treatment of presbycusis in older listeners. This work is relevant because it will lead to a better understanding of how the aging process affects the auditory system and will pave the way for unique pharmaceutical and technological interventions that prevent, slow down, or reverse this pervasive age-related medical condition.